Nouvelles indications/ Nouvelles valves

Transcription

1 Nouvelles indications/ Nouvelles valves Sadra Lotus Valve system Boston Scientific A. Tirouvanziam Institut Thorax Nantes SH AC Sept 2012 Slide 1 of 53

2 SH AC Sept 2012 Slide 2 of 53

3 Building on Success First generation devices provide significant clinical benefit, but opportunities for improvement remain: Improve placement accuracy Allow atraumatic aortic/ventricular repositioning Decrease perivalvular leakage Simplify preparation and loading of valve Permit atraumatic retrieval Decrease complication rate SH AC Sept 2012 Slide 3 of 53

4 SH AC Sept 2012 Slide 4 of 53

5 REPRISE Clinical Program REpositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve SystEm Studying the Safety and Performance of the Lotus Aortic Valve System Percutaneous aortic valve with the design goal to facilitate predictable, accurate placement of the valve prosthesis, while enabling repositioning or retrieval if necessary The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 5 of 53

6 The Lotus Valve System Product Details and Design Goals Device Delivery Nitinol valve frame No balloon inflation or rapid pacing of heart for insertion Introducer sheath same outer diameter as commercially available 18F sheaths Device Positioning Self-centering Controlled positioning for accurate placement Fully retrievable (before release) Valve begins functioning early in deployment process Device Implant Bovine pericardium tri-leaflet aortic valve Adaptive Seal conforms to irregular surfaces of native anatomy to minimize perivalvular leaks The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 6 of 53

7 The Lotus Valve System Components and Function Nitinol Frame designed for repositioning and retrieval Center Marker marks the center of the implant during and after deployment Locking Mechanism Bovine Pericardium proven long-term material Adaptive Seal designed to conform to irregular anatomical surfaces, and to minimize perivalvular leaks The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 7 of 53

8 Lotus Valve System Braided Nitinol Stent Structure Radial expansion as it shortens Design Goals: More flexible delivery system Predictable, accurate placement Repositionable Retrievalable Significant radial strength The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 8 of 53

9 The Lotus Valve System Delivery System Design Goal: Ease of Use Retrievable Valve System Release Deploy, Lock Unlock, Retrieve 2 controls Release Pre-Loaded System Easy to Prepare The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 9 of 53

10 The Lotus Valve System Product Design Goals and First Generation Devices Edwards Sapien XT Medtronic CoreValve BSC / Sadra Lotus Pre-loaded Delivery System Reversibility of Deployment partial 1 18F Profile Paravalvular Sealing Component Leaflet Material Bovine Porcine Bovine 1. Retrievable up to and including full deployment, and prior to the implant release from the delivery system. Other Sources: Edwards.com, Medtronic.com, Sadramedical.com; The Lotus Valve System is an investigational device, not available for sale. CoreValve is an investigational device in the U.S., and not approved for sale. SH AC Sept 2012 Slide 10 of 53

11 REPRISE Clinical Program Objectives To assess the acute safety and performance of the Lotus Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic patients with calcified stenotic aortic valves who are considered high risk for surgical valve replacement. REPRISE I Feasibility Study Design Primary Endpoint Valve size Prospective, single-arm, feasibility study Clinical procedural success: Device Success without in-hospital MACCE thru discharge or 7d post-procedure Defined as device success (VARC definition) without in-hospital MACCE 23 mm N 11 patients in Australia Royal Adelaide Prof. Stephen Worthley St. Vincent s Hospital Prof. Rob Whitbourn Monash Medical Center Prof. Ian Meredith (Principal Investigator) The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 11 of 53

12 Study Flow Intent-To-Treat Population Intent-To-Treat (N=11) Lotus Valve Implanted (N=11) No Lotus Valve Implanted (N=0) Death before Discharge/7 Days (N=0) No Discharge/7 Days Clinical f/u (N=0) Discharge/7 Days Clinical f/u or Death 100% (11/11) Discharge defined as discharge of hospitalization or 7 days post-procedure (whichever comes first) The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 12 of 53

13 REPRISE I Key Inclusion Criteria Age 70 years Documented calcified native aortic stenosis AVA <1.0 cm² (or AVA index <0.6 cm²/m²) plus either MPG >40 mmhg or jet velocity >4 m/s (by echocardiography) High risk for surgical AVR STS score 8% or euroscore 20% or documented heart team agreement of high risk due to frailty or comorbidities Symptomatic aortic valve stenosis with NYHA Class II Aortic annulus size mm 23 mm valve size used in study AVA=aortic valve area; MPG=mean pressure gradient; NYHA=New York Heart Association; STS=Society of Thoracic Surgeons SH AC Sept 2012 Slide 13 of 53

14 REPRISE I Key Exclusion Criteria Anatomic Unicuspid or bicuspid aortic valve >2+ mitral or >2+ aortic regurgitation; prosthetic valve (any location) or ring Left ventricular ejection fraction <30% Femoral artery lumen <6.0 mm or iliac-femoral tortuosity/calcification precluding safe sheath insertion Clinical Acute myocardial infarction within 30 days CVA or TIA within 6 months or any permanent neurologic defect Dialysis dependent or Cr >3.0 mg/dl Cardiogenic shock or hemodynamic instability (e.g., requiring inotropic support) Any therapeutic invasive cardiac procedure within 30 days Gastrointestinal bleed within 3 months Life expectancy <12 months due to non-cardiac, co-morbid conditions SH AC Sept 2012 Slide 14 of 53

15 Baseline Patient Characteristics REPRISE I (N=11) Characteristic Patients Age (Years) 83.0±3.6 Gender (Female) 11/11 STS Score (%) 4.9±2.5 Logistic euroscore (%) 9.5±4.4 NYHA Class III or IV 5/11 Diabetes, medically treated 2/11 Hypertension, medically treated 10/11 History of coronary artery disease 5/11 History of PCI or CABG 2/11 History of cerebrovascular accident 2/11 Atrial fibrillation 5/11 Values are mean±sd or n/n SH AC Sept 2012 Slide 15 of 53

16 Echocardiographic Measurements REPRISE I - Baseline (N=11) (Core Lab) Parameter Patients Aortic valve area (cm 2 ) 0.7±0.2 Mean aortic valve gradient (mm Hg) 53.9±20.9 Peak aortic gradient (mm Hg) 90.5±30.6 Left ventricular end systolic volume (ml) 24.9±6.6 Left ventricular end diastolic volume (ml) 66.9±11.6 Left ventricular ejection fraction (%) 62.3±7.6 Mitral regurgitation (moderate/severe) 3/11 Aortic regurgitation (moderate/severe) 4/11 Values are mean±sd or n/n SH AC Sept 2012 Slide 16 of 53

17 Procedural Characteristics REPRISE I (N=11) Measure Outcome Total procedure time (min) 110.4±34.7 Total fluoroscopy time (min) 36.9±8.8 Total contrast used (cc) 200±74.3 Lotus Valve implanted 11/11 Symptomatic coronary obstruction 0/11 Successful valve repositioning, if attempted 1 4/4 Successful valve retrieval, if attempted 1 N/A Values are mean±sd or n/n 1. Secondary endpoint The Lotus Aortic Valve replacement system is an investigational device, not available for sale. SH AC Sept 2012 Slide 17 of 53

18 Primary Endpoint Discharge/7 Days REPRISE I (N=11) Measure Patients Clinical Procedural Success (per patient) 9/11 Device Success 10/11 Successful access, delivery, deployment, valve positioning, delivery system retrieval 11/11 Intended valve performance 1 10/11 One valve implanted 11/11 No MACCE through discharge or 7 days 2 10/11 1. AVA >1.0 cm 2 plus either a mean aortic valve gradient <20 mmhg or peak velocity <3m/sec, without moderate/ severe prosthetic valve aortic regurgitation 2. Major adverse cardiovascular or cerebrovascular events including all-cause mortality, peri-procedural MI 72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction Values are n/n SH AC Sept 2012 Slide 18 of 53

19 Mean Aortic Gradient by Patient REPRISE I (N=11) Mean Gradient (mm Hg) Mean: Patient B Normal <20 (VARC) Mean: Pre-Procedure Discharge VARC=Valve Academic Research Consortium; J Am Coll Cardiol 2011, 57:253 SH AC Sept 2012 Slide 19 of 53

20 Aortic Valve Area by Patient REPRISE I (N=11) Aortic Valve Area (cm 2 ) Patient B Mean: Mean: Normal >1.2 (VARC) Pre-Procedure VARC=Valve Academic Research Consortium; J Am Coll Cardiol 2011, 57:253 Discharge is defined as discharge or 7 days post-procedure, whichever comes first Discharge SH AC Sept 2012 Slide 20 of 53

21 TTE Data at Baseline & Discharge/7 Days REPRISE I Measurement Baseline (N=11) Discharge (N=11) Peak aortic velocity (cm/sec) 471.0± ±31.2 Peak aortic gradient (mm Hg) 90.5± ±6.8 Mean aortic gradient (mm Hg) 53.9± ±3.7 Aortic valve area (cm 2 ) 0.7± ±0.2 LVEF (%) 62.3± ±6.6 LV end systolic volume (ml) 24.9± ±6.2 LV end diastolic volume (ml) 66.9± ±7.7 Mitral regurgitation (mod/severe) 3/11 3/11 Discharge is defined as discharge or 7 days post-procedure, whichever comes first. Values are mean±sd or n/n. SH AC Sept 2012 Slide 21 of 53

22 MACCE REPRISE I Discharge/7 Days (N=11) Characteristic Patients In-hospital MACCE 1/11 All cause mortality 0/11 Peri-procedural MI ( 72 hours) 0/11 Major stroke 1 1/11 Urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction 0/11 1. Preliminary adjudication is major stroke; final adjudication per VARC will occur at 90 days Discharge is defined as discharge or 7 days post-procedure, whichever comes first. MACCE=major adverse cardiovascular and cerebrovascular events; MI=myocardial infarction SH AC Sept 2012 Slide 22 of 53

23 Additional Clinical Outcomes -1 REPRISE I Discharge/7 Days (N=11) Characteristic Patients Minor Stroke 0/11 Transient ischemic attack 0/11 Myocardial infarction 0/11 Acute kidney injury 1 1/11 Stage 1 1/11 Stage 2 or 3 0/11 1. Change in serum creatinine ( 72 h) compared to baseline Stage 1: Increase in serum creatinine to % of baseline or increase of 0.3 mg/dl ( 26.4 μmol/l) Stage 2: Increase in serum creatinine to % of baseline or increase between >0.3 mg/dl (>26.4 μmol/l) & <4.0 mg/dl (<354 μmol/l) Stage 3: Increase in serum creatinine to 300% of baseline or serum creatinine of 4.0 mg/dl ( 354 μmol/l) with an acute increase 0.5 mg/dl (44 μmol/l) Discharge is defined as discharge or 7 days post-procedure, whichever comes first SH AC Sept 2012 Slide 23 of 53

24 Additional Clinical Outcomes - 2 REPRISE I Discharge/7 Days (N=11) Characteristic Patients Vascular complications 2/11 Major 1/11 Minor 1/11 Patient A: Major Vascular Complication Left femoral dissection treated with balloon angioplasty; patient also experienced a major stroke Discharge is defined as discharge or 7 days post-procedure, whichever comes first. Images courtesy of Monash Health, Melbourne, Australia. SH AC Sept 2012 Slide 24 of 53

25 Additional Clinical Outcomes - 3 REPRISE I - Discharge/7 Days (N=11) Characteristic Patients Bleeding 3/11 Life threatening/disabling 0/11 Major (not related to TAVR access) 2/11 Minor 1/11 Patient C: Major Bleed Patient developed hematoma at the site of a left brachial arterial line. Baseline Hb 6 days prior to procedure was 12.4 g/dl and nadir was 8.3 g/dl 6 days after procedure. Patient received one unit PRBCs. Patient D: Major Bleed Patient developed hematoma at the site of the right internal jugular vein sheath. Baseline Hb 1 day prior to procedure was 14.6 g/dl and nadir was 9.7 g/dl 2 days after procedure. No transfusion given. Discharge is defined as discharge or 7 days post-procedure, whichever comes first. TAVR=transcatheter aortic valve replacement SH AC Sept 2012 Slide 25 of 53

26 Additional Clinical Outcomes - 4 REPRISE I - Discharge/7 Days (N=11) Characteristic Patients Conduction disturbance requiring new pacemaker 4/11 Pt Baseline Rhythm PR QRS IV Conduction Pacemaker Implant Day Indication E Sinus Normal 5 CHB F Sinus Normal 4 CHB G AF RBBB 0 H Sinus LAFB 4 AF and bradycardia LBBB and bradycardia Discharge is defined as discharge or 7 days post-procedure, whichever comes first SH AC Sept 2012 Slide 26 of 53

27 Primary Endpoint Patient Details REPRISE I Patient A: Major Ischemic Stroke Symptoms: Expressive aphasia and dysphagia post-procedure CT: New parieto-temporal ischemic stroke in left MCA branch MRS=3 at discharge Preliminary adjudication is major stroke; final adjudication per VARC will occur at 90 days Patient B: Gradient/Velocity Criterion Not Met Echo Core Lab: Mean gradient=22 mmhg Peak velocity=328 cm/s Valve appeared to be functioning well (AVA=1.6, LVOT/AO TVI ratio=0.51) Gradient likely increased due to a hyperdynamic state as evidenced by HR=90, increased LVOT flow (LVOT TVI: 28.5cm), relatively high LVEF (67%) and high calculated cardiac output (8 L/m) SH AC Sept 2012 Slide 27 of 53

28 Primary Endpoint Patient B REPRISE I Patient B Mean gradient=22 mmhg Peak velocity=328 cm/s Core lab noted that the valve appeared to be functioning well (AVA=1.6, LVOT/AO TVI ratio=0.51). Images courtesy of Monash Heart, Melbourne, Australia The Lotus Aortic Valve replacement system is an investigational device, not available for sale. SH AC Sept 2012 Slide 28 of 53

29 Aortic Regurgitation REPRISE I Discharge Transthoracic Echocardiography % of Patients n=2 n=1 Severe Moderate Mild n=1 Trivial None n=8 Paravalvular n=10 Central No Moderate / Severe AR by Independent Adjudication N=11 SH AC Sept 2012 Slide 29 of 53

30 REPRISE I Summary Outcomes through Discharge/7 Days (N=11) Clinical procedural success achieved in 9/11patients 1 in-hospital MACCE event (major stroke preliminary adjudication) 1 device failure based on 1 of 4 VARC criteria Paravalvular regurgitation (core lab adjudication at discharge) Mild (n=2) Trivial (n=1) None (n=8) Mean aortic gradient improved from 53.9±20.9 mm Hg (baseline) to 13.7±3.7 mm Hg (discharge) There were no deaths 1. Final adjudication per protocol will occur at 90 days Discharge is defined as discharge or 7 days post-procedure, whichever comes first MACCE=major adverse cardiovascular & cerebrovascular events; VARC=Valve Academic Research Consortium SH AC Sept 2012 Slide 30 of 53

31 REPRISE I Conclusions Results support proof of concept with the Lotus Valve Aortic Replacement System Valve can be positioned precisely & successfully with very little aortic regurgitation after placement Low rate of clinical events through discharge Safety & efficacy data support further study in a larger, more rigorous trial The Lotus Aortic Valve replacement system is an investigational device, not available for sale. SH AC Sept 2012 Slide 31 of 53

32 REPRISE Clinical Program Enrollment to begin Q Objectives To evaluate the safety and performance of the Lotus Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with severe calcific aortic stenosis who are considered high risk for surgical valve replacement REPRISE II CE Mark Primary Endpoint Device Performance Endpoint: Mean aortic valve pressure gradient at 30d Safety Endpoint: All-cause mortality at 30d Valve size 23 and 27 mm N 120 patients Sites 15 sites in Australia, France, Germany, UK PI Prof. Ian Meredith The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 32 of 53

33 Conclusions Aortic valve replacement is a life saving treatment for severe aortic stenosis Transcatheter aortic valve replacement (TAVR) has been shown to be a viable alternative to surgery for patients at high or extreme risk for surgical intervention TAVR with first generation devices is a technically challenging procedure with a relatively high rate of periprocedural complications New technology promises to improve outcomes and usability of first generation TAVR systems As reflected in the REPRISE I Trial, The Lotus Valve System is designed to address current challenges via its Adaptive seal and its repositionable deployment mechanism The Lotus Valve System is an investigational device, not available for sale. SH AC Sept 2012 Slide 33 of 53